When one becomes more: minimum renal artery length in laparoscopic live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into multiple arteries, increasing the technical challenge of implantation. We evaluated our experience to identify factors predictive of multiple arteries after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the start of our program in November 2002 until June 2013 were studied, and preoperative imaging reviewed for donor artery length and multiplicity together with operative findings. RESULTS: A total of 287 consecutive laparoscopic live donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal artery length was measured from preoperative donor magnetic resonance or computed tomography angiogram and nephrectomy performed using a laparoscopic stapling device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and 16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and 26 mm) on imaging resulted in multiple renal arteries at implantation. Complex renal vein anatomy was associated with multiple arteries following retrieval. CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm on the right is unlikely to result in multiple arteries to implant. The possibility of multiple arteries should be borne in mind when the donor renal artery is short.

Cystic fibrosis liver disease: to transplant or not to transplant?

Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardio-respiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1- and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome.

Adult duodenal intussusception associated with congenital malrotation.

Enteroenteric intussusception is a condition in which full-thickness bowel wall becomes telescoped into the lumen of distal bowel. In adults, there is usually an abnormality acting as a lead point, usually a Meckels' diverticulum, a hamartoma or a tumour. Duodeno-duodenal intussusception is exceptionally rare because the retroperitoneal situation fixes the duodenal wall. The aim of this report is to describe the first published case of this condition. A patient with duodeno-duodenal intussusception secondary to an ampullary lesion is reported. A 66 year-old lady presented with intermittent abdominal pain, weight loss and anaemia. Ultrasound scanning showed dilated bile and pancreatic ducts. CT scanning revealed intussusception involving the full-thickness duodenal wall. The lead point was an ampullary villous adenoma. Congenital partial (type II) malrotation was found at operation and this abnormality permitted excessive mobility of the duodenal wall such that intussusception was possible. This condition can be diagnosed using enhanced CT. Intussusception can be complicated by bowel obstruction, ischaemia or bleeding, and therefore the underlying cause should be treated as soon as possible.

F18-FDG-PET evaluation of patients for resection of colorectal liver metastases.

BACKGROUND/AIMS: Liver resection is the only treatment which offers long-term survival for patients with colorectal liver metastases. However, the significant mortality and morbidity associated with hepatectomy makes accurate patient selection paramount. Current staging by CT and MRI has limitations, with these modalities delivering a sensitivity and specificity of only 70-80%. Thus some patients may be deprived of long-term survival, and others subjected to futile surgery. METHODOLOGY: We report our experience of the influence of F18-FDG-PET scanning in the management of 31 consecutive patients with colorectal liver metastases referred for liver resection. RESULTS: F18-FDG-PET scanning detected liver and pulmonary metastases with a sensitivity of 96% and 100% respectively, in comparison to corresponding figures of 70% and 83% for CT. Furthermore, the sensitivity of F18-FDG-PET scanning in identifying extra-hepatic and extra-pulmonary disease was 100% in comparison to 20% for CT. Overall, F18-FDG-PET scanning resulted in a significant alteration of management in 29% of patients. CONCLUSIONS: F18-FDG-PET scanning has an important clinical impact on the management of patients being considered for resection of colorectal liver metastases.

Results with combined kidney and paratopic segmental-pancreas transplantation.

Rehabilitation and quality of life after combined pancreas and kidney transplantation was assessed in 15 previously diabetic patients in renal failure and compared with 11 diabetic patients in renal failure transplanted with a kidney only. The paratopic segmental-pancreas-grafting technique, which allows physiologic insulin delivery into the portal venous system, was used in 13 patients; 2 patients received a heterotopic segmental-pancreas graft, resulting in systemic insulin delivery. A kidney was transplanted heterotopically in all cases. Mean age, duration of diabetes, retinopathy, neuropathy, mortality, infection rate, and immunosuppressive treatment did not differ significantly between the groups. Diabetic patients with only kidney transplants had difficulties adjusting to their diabetes, which may be partly due to the immunosuppressive treatment. The quality of life only marginally improved. In contrast, patients with a combined pancreas-kidney graft achieved full rehabilitation within a short time.

Examination of the role of the impermeants lactobionate and raffinose in a modified UW solution.

Rat liver transplants were performed in order to assess the importance of the impermeant anion lactobionate and the trisaccharide raffinose on the effectiveness of a simplified variant of UW solution for liver preservation by simple cold storage. Rat livers were stored at 4 degrees C for 18, 24, 30, or 40 hr in a modified UW solution or in one of three variants of UW in which one of these impermeants was replaced by another more permeable agent. Using modified UW solution (solution A), 50% (5/10) of rats receiving livers that had been preserved for 30 hr survived for more than 1 week; with solution B, which differs from A in the replacement of raffinose by glucose, the 1-week survival was 60% (6/10) after 30-hr preservation. Solution C, which is identical to A except for the replacement of lactobionate by gluconate, gave 20% (2/10) survival rate after 30-hr preservation. However, using solution D, which is identical to A except for substitution of chloride for lactobionate, none (0/8) of the rats receiving liver preserved for 30 hr survived. These results suggest that the inclusion of lactobionate as a major anion plays a crucial role in the effectiveness of UW solution, whereas raffinose can be replaced by more permeant glucose without deleterious effect.

A comparison of a new solution combining histidine and lactobionate with UW solution and eurocollins for rat liver preservation.

Forty-six rat liver transplants were performed to investigate the effectiveness of a simplified lactobionate solution containing histidine as a buffer (histidine-lactobionate solution) and to compare it with University of Wisconsin solution. This new solution is isoosmotic (320 mOsm/L) and has a higher sodium content and a lower potassium content (Na: 90 mEq/L, K: 45 mEq/L) than standard UW solution. Buffering capacity is increased by adding histidine (90 mM/L) together with KH2PO4 (20 mM/L) and is greater than that of Eurocollins solution or UW solution. Adenosine, insulin, hydroxyethyl starch, and dexamethasone that are included in UW solution are not included in the new solution. The 1-week survival rate of rats transplanted with livers preserved in this solutions at 4 degrees C was 85% (11/13) following 24-hr preservation and 33% (2/6) after 30-hr preservation. By contrast, UW solution gave only a 29% (5/17) survival rate after 24-hr preservation and 0% (0/6) survival after 30-hr preservation, demonstrating that this simplified UW solution with histidine is superior to UW solution in rat liver preservation. No rats (0/4) receiving livers preserved for 24 hr in Eurocollins solution survived. These findings show that the inclusion of histidine as a buffer dramatically improves the effectiveness of lactobionate-based preservation solutions and justify application in a large-animal model and subsequently in clinical liver transplantation.

24-hour rat liver preservation using UW solution and some simplified variants.

The results of a series of 32 rat liver transplants are described to analyze the efficacy of components of UW solution. Rat livers were stored at 4 degrees C in standard UW solution or one of three simplified variants for 24 hr prior to orthotopic liver transplantation. In standard UW solution (solution A) the one-week survival rate was 3 of 8. Using solution B, which differs from solution A in the omission of hydroxyethyl starch and adenosine, the one-week survival rate was 2 of 8. Solution C, a further-simplified version of solution B with omission of allopurinol, Bactrim, and insulin, gave a one-week survival rate of 3 of 8. Solution D is identical to solution B except that the sodium and potassium concentrations are reversed. Using this solution, 5 of 8 rats survived more than one week. We conclude that the effectiveness of UW solution is maintained in a substantially simplified form, and that solution D, with the Na/K ratio reversed to give a high Na variant, may improve survival.

An analysis of the components in UW solution using the isolated perfused rabbit liver.

The isolated perfused rabbit liver model has been used to determine the essential components of the UW solution for hepatic preservation by simple cold storage. Livers were stored on ice for 48 hr after initial flushing with the solution being tested, and then reperfused at 38 degrees C in an isolated perfusion circuit; bile flow and enzyme (SGOT, SGPT, and LDH) release during a 2-hr period were recorded. All solutions tested contained phosphate (25 mM) as a buffer and magnesium sulfate (5 mM). Sodium can be substituted for potassium without adverse effects. Lactobionate, raffinose and glutathione cannot be omitted; all other components can be eliminated without altering the effectiveness of the solution in this model.

An examination of the effects of solutions containing histidine and lactobionate for heart, pancreas, and liver preservation in the rat.

Fifty-five rat pancreas transplants, 18 rat heart transplants, and 41 rat liver transplants were performed using standard UW solution, the new HL solution (HL-I), or a modified HL solution (HL-II). Storage times of 18 hr were used in the heart preservation experiments, 24 hr in the liver preservation experiments, and 48 or 72 hr in the pancreas preservation experiments. HL-I solution was superior to both HL-II and UW solution for heart preservation (1-week graft survival rates of 100% [7/7], 0% [0/5], and 50% [3/6], respectively). HL-I and HL-II were superior to UW for 24 hr liver preservation (1-week graft survival rates of 78% [11/14], 80% [8/10], and 29% [5/17], respectively). In contrast, HL-II was superior to both HL-I and UW solutions for pancreas preservation following both 48-hr preservation and 72-hr preservation. Satisfactory graft function was achieved in 100% (7/7), 40% (6/15), and 44.4% (4/9) of pancreases transplanted after 48 hr using HL-II, HL-I, and UW solutions, respectively, and in 50% (4/8), 0% (0/8), and 0% (0/8) following 72-hr preservation. Histidine- and lactobionate-containing solutions thus represent a further improvement in organ preservation by simple cold storage.

Rat liver blood flow after ischemia and reperfusion. The effects of the platelet-activating factor antagonist WEB-2170 and of removing circulating leukocytes.

The inflammatory response to trauma induces release of platelet activating factor (PAF), which promotes leukocyte adherence to the vascular endothelium. Ischemia and reperfusion induces inflammatory reactions that play a role in reperfusion injury, and here we investigate the role of both PAF and of leukocytes in damage to reperfused rat liver. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver in vivo, and subsequent reperfusion after defined periods. Rats were pretreated either with the PAF-antagonist WEB-2170 or with vinblastine to induce leukopenia, and compared with controls. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using an He-Ne Laser doppler flowmeter and photometer. Reperfusion after 30 and 45 min of ischemia was associated with partial recovery to normal values and was inversely proportional to the duration of ischemia. In the WEB-2170-treated group, liver flow and hemoglobin saturation upon reperfusion did not show significant differences when compared with the untreated control groups, suggesting that inhibition of PAF activity did not protect against the microcirculatory disturbance induced by ischemia and reperfusion in the liver. In contrast, rats made leukopenic by treatment with vinblastine showed significantly better recovery of blood flow and hemoglobin saturation than the control group after 45 min of ischemia. Thus, we found that although PAF alone did not appear to have a pivotal role in the cascade of reperfusion injury, the effect of leukocytes is critical.

Regulation of the complement cascade by soluble complement receptor type 1. Protective effect in experimental liver ischemia and reperfusion.

The complement cascade was inactivated in a model of rat liver ischemia with the purpose of studying the role of complement in tissue injury after ischemia and reperfusion. Soluble human complement receptor type 1 (sCR1) was administered either in a single dose of 25 mg/kg or in 2 doses of 50 mg/kg i.v. over 24 hr after vascular occlusion. Sham-operated rats, nontreated rats submitted to liver ischemia, and rats pretreated with cobra venom factor and submitted to liver ischemia were used as controls. This experiment consists of the temporary interruption of arterial and portal blood flow to the left lateral and medial lobes of the liver for 45 min, followed by a 24-hr period of follow-up after reperfusion. Liver blood flow and hemoglobin saturation were recorded for 1 hr after declamping, with statistically significant differences between the experimental groups and the untreated control group, which received liver ischemia (P < 0.001). At 24 hr, galactose elimination was assayed as a liver function test; it was significantly better in the sCR1-treated rats when compared with control rats submitted to ischemia (P < 0.01). Alanine aminotransferase levels were also significantly lower in the sCR1-treated rats at 6 and 24 hr (P < 0.05). Complement activity was reduced to 25% and 12.5% of normal rats with the respective doses of sCR1. Immunoperoxidase stainings for C3 and C9 were performed on liver sections; they showed endothelial deposits of C3 and C9 in the control group subjected to ischemia. Few C3 deposits were present in the sCR1 (25 mg/kg)-treated rats, but not in the cobra venom factor or sCR1 (50 mg/kg) groups. These results confirm that complement is inactivated by sCR1 with amelioration of reperfusion injury in the rat liver.

Radionuclide studies in intestinal transplantation. Diagnosis of rejection and assessment of permeability.

Three patients who received intestinal allografts were studied using two distinct radionuclide investigations. In the first, 111In or 99mTc-labeled leukocyte scanning was performed to assist in the diagnosis of rejection. It was able to demonstrate the occurrence of rejection in the transplanted intestine, and the response to antirejection therapy. In 1 case, the abnormality on the scan preceded the histological confirmation of rejection. The second technique studied mucosal integrity by serial 51Cr-EDTA/14C-mannitol permeability tests. These studies demonstrated the initial marked impairment and the slow return to normal function of the intestinal mucosal barrier. In 1 patient, this occurred by 91 days; in another, it took 232 days. A single assay performed in the third patient at the time of allograft rejection was also abnormal. Both radionuclide tests were helpful in the care of these complicated cases.

Preservation of the canine liver for 24-48 hours using simple cold storage with UW solution.

The results of a series of 29 orthotopic liver transplants in the dog are described. The livers were preserved in a new cold storage fluid, UW solution, and were successfully transplanted after periods of storage of 24, 30, 36, and 48 hr. All six animals transplanted after 24 hr survived beyond 5 days after transplantation and had excellent graft function. Four of six survived for at least 5 days after 30 hr of cold storage, and five of five after 36 hr. Five of six consecutive dogs that received transplants that had been cold-stored for 48 hr survived for 5 or more days. This solution represents a substantial advance over all existing cold storage solutions for liver preservation.

A comparison of some simplified lactobionate preservation solutions with standard UW solution and Eurocollins solution for pancreas preservation.

Fifty-two rat pancreas transplants were performed to investigate which components of the UW solution were essential for successful pancreas preservation. LEW rats were used and the pancreata stored at 4 degrees C for 48 hr after flushing with commercial UW solution (ViaSpan, DuPont Pharmaceuticals) or a number of simplified solutions. Following storage the pancreata were transplanted into syngeneic recipient animals with streptozotocin-induced diabetes mellitus. Graft function was assessed by regular postoperative blood sugar measurements and a glucose tolerance test on the 14th postoperative day. With commercial UW solution, 4 of 9 recipients (44%) showed satisfactory graft function, while only one of 5 pancreata preserved using Eurocollins solution demonstrated satisfactory function. With solution A, in which hydroxyethyl starch and insulin were omitted from the standard UW solution, 3 of 7 recipients (43%) showed satisfactory function. Omission of glutathione, allopurinol, and adenosine from this solution (solution B) gave satisfactory function in 4 of 8 cases (50%). Substitution of raffinose in solution B with an equimolar concentration of glucose (solution C) resulted in acceptable function in 5 of 8 cases (62%). Increasing the raffinose concentration in solution B to 100 mM/L resulted in only 2 of 8 grafts (25%) with adequate function. By contrast, reversing the Na/K concentrations in solution A resulted in 100% (7/7) satisfactory graft function. We conclude that the rat pancreas can be successfully transplanted following 48-hr cold preservation using UW solution and some simplified versions, and that a substantially simplified lactobionate-based solution with a reversed sodium/potassium ratio improved survival.

CsA levels in the early posttransplant period--predictive of chronic rejection in liver transplantation?

The increasing success of clinical liver transplantation has brought rejection to the forefront as a cause of morbidity and graft loss. The relationship of immunosuppressive drug doses and levels to acute and chronic rejection remains a matter of debate. The effect of blood CsA levels and drug doses on the incidence of acute and chronic rejection and the impact of acute rejection episodes on the occurrence of chronic rejection were studied in 146 grafts in 132 patients. These patients were transplanted in the 4-year period from June 1989 using CsA-based immunosuppression (CsA, azathioprine, prednisolone). Liver grafts in patients maintained on median CsA levels (whole blood, trough level) of > or = 175 micrograms/L in the first 28 days posttransplant had a significantly lower incidence of chronic rejection (2 out of 49 vs. 22 out of 97; P = 0.002). There was no significant difference in incidence of graft loss due to fatal sepsis (6% vs. 5%) or nephrotoxicity between the high and low CsA level groups. The overall graft loss rate was lower in the higher CsA level group (22% vs. 37%). The total doses of the individual drugs did not correlate with the incidence of acute or chronic rejection. Although the occurrence of acute rejection itself did not determine later chronic rejection, late occurrence (P < 0.00001) and multiple episodes (two or more; P = 0.0002) of acute rejection were significant risk factors for the occurrence of chronic rejection. We conclude that to minimize graft loss to rejection, CsA levels should be maintained at greater than 175 micrograms/L in the early posttransplant period, and late and recurrent episodes of acute rejection should be prevented.

Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients.

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.

Sirolimus: a potent new immunosuppressant for liver transplantation.

BACKGROUND: Sirolimus (rapamycin) is a new immunosuppressant that appears to be synergistic with cyclosporine in kidney transplantation, but with a different side-effect profile. This pilot study evaluated sirolimus in liver transplantation. METHODS: Patients undergoing orthotopic liver transplantation for primary tumors (8), and later for nonmalignant disease (7), received one of three sirolimus-based immunosuppressive regimens. Protocol A comprised sirolimus, microemulsion cyclosporine (target whole blood concentration: 100 ng/ml), and prednisolone; protocol B omitted prednisolone; and protocol C was sirolimus alone. By 3 months after transplantation, all patients were receiving sirolimus as monotherapy. RESULTS: Fifteen patients were treated with a follow-up of 117-806 days. Rejection was more common on monotherapy than double therapy, and absent on triple therapy. The drug was generally well tolerated, with only three patients discontinuing sirolimus: one for hyperlipidemia, one for pneumocystis pneumonia, and one for inability to tolerate the taste of the drug. Two patients discontinued cyclosporine early, both as a result of neurological complications; they continued on sirolimus monotherapy. Five patients died; one suffered a cardiac arrest, and four died from sepsis in association with graft-versus-host disease, recurrent tumor, a paralyzed right hemidiaphragm, and primary nonfunction. CONCLUSIONS: Sirolimus combined with cyclosporine provided potent immunosuppression of liver allografts, and sirolimus monotherapy was adequate and well tolerated as maintenance therapy. Side effects of sirolimus over the short period of follow-up were uncommon and reversible with dose reduction or cessation of therapy.

Review article: improved preservation of the liver for transplantation.

This paper reviews the development of the techniques used for liver preservation and describes their clinical use. Recent advances with the introduction of lactobionate based solutions for simple cold storage are described and illustrated by their effect on the Cambridge/King's College Hospital transplant programmes. Better preservation of the liver has simplified the logistics of the transplant procedure, improving organ usage and allowing increased sharing of livers for urgent or paediatric cases.